Z-phenyl-j-methyl-z



United dtates Patent 2-PHENYL-3-METHYL-2,3-DIHYDROXY- HEXENES-(S) PeterWerner Feit, Kongens Lyngby, Denmark, assignor to Lvens kemiske Fabrikved A. Kongsted, Copenhagen, Denmark No Drawing. Application July 1,1958 Serial No. 745,815

Claims priority, application Great Britain July 12, 1957 1 Claim. (Cl.260618) This invention relates to 2-substituted3-methyl-2,3-dihydroxyhexenes-(S) having the general formula:

CH3 CH3 OH H in which X denotes hydrogen or chlorine. Thus, the newcompounds produced according to the invention are 2-phenyl-3-methyl-2,3-dihydroxyhexene-(5) and its pchloro-derivative.

These compounds are hitherto unknown substances. They are useful assedatives, particularly as tranquilizers. In biological tests with smallmammals it has been found that the compounds are capable of exerting along lasting sedative action producing muscular relaxation, and, withlarger doses, loss of righting reflexes. Furthermore, they produceblocking of polysynaptic reflexes in the spinal cord of cats, but exertno action on monosynaptic reflexes, on the myoneural junction or on theconduction in peripheral nerves.

The new compounds compare favourably with known tranquilizers, such as2-methyl-2-n-propyl-1,3-propanediol dicarbamate (meprobamate) and2-p-chlorophenyl- 3-methyl-2,3-butanediol (phenaglycodol) in theireffectiveness in prolonging sleep produced by 1,5-dimethyl-5-(l-methylbutyl)-barbituric acid (hexobarbital). Thus,2-phenyl-3-methyl-2,3-dihydroxyhexene-(5) has shown about four times thepotency of meprobamate in this test.

Clinical experience has shown that 2-penyl-3-methyl-2,3-dihydroxyhexene-(5) compares favourably with meprobamate as a tranquilizer for male and female patients in the age range from 67 to 89years suffering from senile psychic disturbances, such as depressions,confusions, restlessness and excitements. In 28% of the casesimprovements superior to those obtained with meprobamate were observed,whereas in 22% of the cases the two medicaments produced equalimprovements, and in 44% of the cases had no marked tranquilizingeffect. In 6% of the cases meprobamate was superior. The toxicity of the'said two medicaments was found to be practically the same.

The new compounds can advantageously be produced by reacting acompoundisele'cted from the group consisting of Z-phenyl andZ-p-chlorophenylacetoin with a compound selected from the groupconsisting of 2- pro penyl-magnesium chloride and bromide anddecomposing the Grignard-compound thereby formed to the desired compoundand magnesiumhydroxy chloride or bromide, respectively.

The acetoin derivatives used as starting substances by the methodaccording to the invention can be prepared F ICC as described in thefollowing direction for the preparation of 2-p-chlorophenylacetoin:

2 g. of mercuric oxyde are dissolved in 20 ml. of 4 N sulphuric acid,and the solution'is mixed with 30 ml. of methanol. To the mixture, asolution of 20 g. of pchlorophenyl-methyl-ethinyl-carbinol (prepared inthe known manner by reacting p-chloroacetophenone with acetylene) in 10ml. of methanol is added dropwise at 60-65 C, during one and a halfhours, and the mixture is kept at the said temperature for 3 hours.Then, 10 g. of potassium carbonate are added slowly, and the mixture iscooled. The resulting ketone is extracted with ether, and the etherealsolution is Washed with water and dried over MgSO The ether isevaporated, and the residue is fractionated in vacuo, yielding 15.5 g.of Z-p-chlorophenylacetoin, a hitherto unknown compound boiling atl47l48 C. at a pressure of 10 mm. of mercury.

2-phenylacetoin can be prepared in an analogous manner.

EXAMPLE 1 2-propenyl-magnesium chloride is prepared in known manner from12 g. of magnesium and 34.5 g. of 3- chloropropene in 120 ml. ofanhydrous ether. To the resulting suspension, a solution of 16.4 g. ofZ-phenylacetoin in 100 ml. of anhydrous ether is added slowly at 10 C.with stirring. The. mixture is then heated to 25 C. and stirred at thistemperature for 16 hours, whereafter it is decomposed with an aqueoussolution of ammonium chloride, and the ether phase is separated. Theethereal solution is washed with water, dried over MgSO, and evaporatedto dryness. A partly crystalline residue is obtained, which iscrystallized completely with hexene. After repeated recrystallizationsfrom benzene, the recovered 2-phenyl-3-methyl-2,3-dihydroxyhexcue-(5)melts at 9898.5 C.

EXAMPLE 2 hexene- (5 2-propenyl-rnagnesium chloride is prepared in knownmanner from 6 g. of magnesium and 17.25 g. of 3} chloropropene in 60 ml.of anhydrous ether. To the resulting suspension, a solution of 10 g. of2-p-chlorophenylacetoin in 50 ml. of anhydrous ether is added slowly at10 C. with'stirring. The mixture is then heated to 25 C. and stirred atthis temperature for 16 hours, whereafter it is decomposed with anaqueous solution of ammonium chloride, and the ether phase is separated.The ethereal solution is washed withwater, dried over MgSO, andevaporated to dryness. A partly crystalline residue is obtained, whichis crystallized completely with hexane. After repeated recrystallizations from hexane and benzene, the recovered2-p-ch1orophenyl-3methyl-2,3-dihydroxyhexene-(5) melts at 104.5- 105.5C. J

I claim: A member of the group consisting of 2-phenyl-3-methyl-2,3-dihydroxyhexene-(5) and its .p-chloro-derivative.

References Cited in the file of this patent Pansevich-Kolyada et al.:Chem. Abstracts, vol. 49 (1955), col. 6173-74 (1 page). a

